Preterm births and deaths: from counting to classification
Authors: Deepak Chawla, Ramesh Agarwal
Journal: The Lancet Global Health (2022)

One in ten babies worldwide is born before completing 37 weeks of gestation, resulting in 15 million preterm births every year.1March of DimesPMNCHSave The ChildrenWHOBorn too soon: the global action report on preterm birth.http://apps.who.int/iris/bitstream/handle/10665/44864/9789241503433_eng.pdf;jsessionid=D8CC67C1F932134E421D81B3846A383A?sequence=1Date: 2012Date accessed: September 11, 2022Google Scholar Preterm birth and related complications cause 1 million child deaths every year. Many others suffer from prematurity-related morbidities and resultant long-term adverse effects on nutritional status, brain development, and lung functions. The incidence of preterm birth is increasing in many regions of the world.2Cao G Liu J Liu M Global, regional, and national incidence and mortality of neonatal preterm birth, 1990–2019.JAMA Pediatr. 2022; 176: 787-796Crossref PubMed Scopus (49) Google Scholar However, strategies to prevent preterm birth and improve the evidence-based care of neonates need to recognise that preterm birth is not a single disease but an umbrella term used to describe a health status resulting from a multitude of known and unknown environmental and genetic factors. We can classify prematurity based on how soon a baby is born or on maternal, placental, and fetal pathologies contributing to preterm birth. The Global Alliance to Prevent Prematurity and Stillbirth has suggested a classification system that recognises preterm birth as a syndrome with overlapping contributions of maternal, placental, and fetal conditions. It considers the signs of initiation of parturition and pathway to delivery to classify preterm neonates into different clusters.3Villar J Papageorghiou AT Knight HE et al.The preterm birth syndrome: a prototype phenotypic classification.Am J Obstet Gynecol. 2012; 206: 119-123Summary Full Text Full Text PDF PubMed Scopus (177) Google Scholar In various studies, the clinical application of the classification system has recognised distinct phenotypic groups of preterm birth.4Maghsoudlou S Beyene J Yu ZM McDonald SD Phenotypic classification of preterm birth among multiparous women: a population-based cohort study.J Obstetrics Gynaecol Can. 2019; 41: 1433-1443Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 5Barros FC Papageorghiou AT Victora CG et al.The distribution of clinical phenotypes of preterm birth syndrome: implications for prevention.JAMA Pediatr. 2015; 169: 220-229Crossref PubMed Scopus (105) Google Scholar However, in about a third of cases, there were no maternal, placental, or fetal causes of preterm births, possibly due to incomplete evaluation for placental histopathology, subclinical chorioamnionitis, or fetal–neonatal infection. The available literature also lacks studies from low-income and middle-income countries with the highest burden of preterm births and deaths. With the project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe) study, published in this issue of The Lancet Global Health, Sangappa M Dhaded and colleagues attempt to fill this gap.6Dhaded SM Saleem S Goudar SS et al.The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.Lancet Glob Health. 2022; 10: e1575-e1581Summary Full Text Full Text PDF Scopus (5) Google Scholar Although limited to five health facilities in India and Pakistan that might not represent the preterm birth epidemiology in resource-limited settings, the study adds several important insights into the causes of deaths associated with preterm birth. First, in about a third of neonatal deaths, the mothers had hypertensive disorders (204 [33%] of 615 cases), the placenta showed corresponding vascular maladaptive changes (172 [28%]), and the neonates had evidence of intrauterine hypoxia (212 [34%]).6Dhaded SM Saleem S Goudar SS et al.The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.Lancet Glob Health. 2022; 10: e1575-e1581Summary Full Text Full Text PDF Scopus (5) Google Scholar This finding highlights the need for high-quality antenatal care that can identify women with macronutrient and micronutrient deficiencies or gestational hypertension, and institute measures of maternal nutritional rehabilitation, fetal surveillance, and appropriate delivery time. Second, the study reports evidence of congenital infections (ie, those acquired before delivery) and of neonatal infections (ie, those acquired after delivery) in about 20% of neonatal deaths.6Dhaded SM Saleem S Goudar SS et al.The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.Lancet Glob Health. 2022; 10: e1575-e1581Summary Full Text Full Text PDF Scopus (5) Google Scholar Importantly, unlike hypertension, corresponding findings of infective pathology were not detected clinically in mothers. This finding highlights the need for studies evaluating the epidemiology of maternal genital tract colonisation or infections in preterm births. Evidence-based strategies are needed to detect pregnant women with abnormal reproductive tract colonisation or infection and administer intrapartum antibiotic prophylaxis. Using appropriate antimicrobial agents for intrapartum antibiotic prophylaxis can potentially reduce the incidence of neonatal infections, reduce the use of antibiotics in neonates, and contribute to stemming the burgeoning antimicrobial resistance. Since group B streptococcus was not a common pathogen, an intrapartum antibiotic prophylaxis approach to target bacterial flora specific to the scenario in low-income and middle-income settings is needed. Third, in PURPOSe, of all neonatal deaths during the study period, about a quarter (189 of 804) were excluded as their birthweight was less than 1000 g. This is not a small number that can be ignored. Extremely low birthweight can result from extreme prematurity, fetal growth restriction, or both. This is a distinct subpopulation of preterm neonates that needs to be included in future studies to evaluate the contribution of different maternal, placental, and fetal pathologies. A complete evaluation of preterm birth phenotypes and the contribution of different factors to preterm deaths should include neonatal deaths and stillbirths at preterm gestation. A comprehensive cohort of preterm births, including stillbirths and livebirths, will genuinely inform public health professionals and policy makers about the population attributable risk for different conditions contributing to prematurity-related deaths. Although PURPOSe has filled an important void in the knowledge about causes of preterm death in resource-limited settings, we believe the study has collected more information that can be useful. Complete diagnostic autopsy of neonatal deaths is rare in resource-limited settings due to logistic and cultural barriers.7Lewis C Hill M Arthurs O Hutchinson C Chitty L Sebire N Factors affecting uptake of postmortem examination in the prenatal, perinatal and paediatric setting.BJOG. 2018; 125: 172-181Crossref PubMed Scopus (66) Google Scholar Although the study tried to overcome this by performing minimally invasive tissue sampling (MITS) in a subset of infants, it would be helpful to know how MITS, tissue histopathology, and microbiological evaluation added to clinically available information about the causes of neonatal death. Finally, many preterm deaths can be averted using evidence-based interventions. However, not all causes leading to preterm birth and death are equally amenable to therapeutic and preventive interventions. It is worth exploring whether there are subgroups that respond more to a given therapeutic interventions to better define cost–benefit ratio.8Räikkönen K Gissler M Tapiainen T Kajantie E Associations between maternal antenatal corticosteroid treatment and psychological developmental and neurosensory disorders in children.JAMA Netw Open. 2022; 5e2228518Crossref PubMed Scopus (7) Google Scholar We declare no competing interests. The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort studyIn south Asia, intrauterine hypoxia and congenital infections were the major causes of neonatal death among preterm babies. Maternal hypertensive disorders and placental disorders, especially maternal and fetal vascular malperfusion and placental abruption, substantially contributed to these deaths. Full-Text PDF Open Access